Semantic memory (SM) contains all of our knowledge of the organization and meaning of the world around us. It supports many complex cognitive operations such as communication and reasoning and plays a decisive role in our daily functioning. At the neuroanatomical level, SM relies on a widely distributed network, which makes it particularly resistant to neuronal decline. It is, in fact, the only memory system that is known to remain stable during normal aging. As a result, the presence of an early semantic decline in older adults is generally observed in a neurodegenerative context, such as in Alzheimer's disease (AD) and in the semantic variant of primary progressive aphasia (svPPA). However, the neurofunctional correlates associated with semantic decline in pathological aging remain to this day poorly understood. Therefore, the main objective of this thesis is to explore the cerebral changes associated with semantic processing in these two neurodegenerative diseases, using magnetoencephalography (MEG) as a method of investigation, in order to document the neurofunctional changes associated with semantic decline, as well as the functional compensatory brain mechanisms that are deployed to allow residual processing when the integrity of the semantic network is compromised. This thesis also aims to determine if common mechanisms of neural plasticity are at play to counteract the effects of semantic deterioration in these two diseases, and to initiate a reflection on the potential clinical implications of these neurofunctional changes. In the context of the subtle SM alterations observed in the prodromal stage of AD, these mechanisms could be reflective of the neuropathological decline even before the emergence of significant structural alterations, highlighting their relevance regarding an early diagnosis. In the case of manifest but relatively circumscribed alteration of SM, such as in svPPA, these mechanisms are informative of the capacity of the compromised semantic network to adjust in order to support residual processing, which can also be useful in deciding which interventions (rehabilitation, palliative) are likely to be most helpful for patients.
The first study (chapter 2) is aimed to investigate the neural correlates underlying semantic disorders in the subclinical stage of AD (aMCI), using a semantic judgment task about famous faces. Our results support the assumption that the pattern of neural alterations observed in aMCI patients is not limited to the hippocampal region, as it extends within several regions of the extended semantic network, including the anterior temporal lobes (ATL). These results also suggest that the pattern of neural dysfunction observed in aMCI patients precedes the emergence of structural alterations within the semantic network, and that the compensatory mechanisms deployed to support the finer semantic processing associated with famous faces in these patients rely notably on an increased recruitment of the right ATL region.
The second study (chapter 3) is aimed to better understand the neural correlates of residual semantic processing in the context of a significant but selective impairment of SM, through the single case study of a svPPA patient, using a semantic categorization task about biological entities and manufactured objects. Despite equivalent behavioral performance, this study revealed a pattern of significant hyperactivation within key regions of the semantic network in the svPPA patient in comparison with controls, extending to the left inferior temporal gyrus and right ATL region. Overall, these findings emphasize that peri-atrophic regions within the ATL may support remaining semantic abilities.
Finally, the last chapter of this thesis (chapter 4) is dedicated to reflect on the clinical and theoretical implications associated with the results of these two studies. The limitations of this thesis and future perspectives are also addressed in this section.